Despite increasing media attention, adult Attention-deficit-hyperactivity disorder (ADHD) has not been systematically studied in large samples. As a result, there has been a debate in the field about the validity of ADHD in adults presenting at mental health clinics. To shed light on this debate, we propose to test hypothesis in one domain of adult ADHD that has received scant attention: its genetic epidemiology. As we review in the background section, there have been only two small pilot studies of the genetic epidemiology of ADHD. Such data are essential to validating the syndrome, creating developmentally appropriate diagnostic algorithms and laying the clinical foundation for genetic linkage studies. To fill this gap in the research literature, we will address the validity of adult ADHD from the genetic epidemiological perspective by testing the following hypothesis for the five main aims of our proposal: 1) Assessing the Familial Transmission of Adult ADHD; 2) Validating Adult ADHD with Molecular Genetic Data; 3) Assessing the Divergent Validity of Adult ADHD; 4) Using Family Study Data to Validate Diagnostic Models of Adult ADHD; AND 5) Creating a Resource for Future Follow-up and Molecular Genetic Studies of Adult ADHD. To acheive these aims, we will complete a double- blind family study of 140 ADHD families and 120 control families. We view our family study strategy as being a valuable investment for several reasons. A large double-blind study of adult ADHD has never been done before. Moreover, because consistent positive associations have been reported between childhood ADHD and two dopamine related genes, the collection of molecular genetic data will allow us to validate adult ADHD at the molecular level. Because we are collecting data about lifetime psychiatric diagnoses, we will be able to determine if other disorders can account for the familial transmission of ADHD or its molecular genetic associations. We will also be able to assess what age at onset criterion and what set of symptom thresholds should be used for the diagnosis of adult ADHD and will be able to define phenotypes and sample selection rules that will maximize the yield of future linkage studies. To maximize the scientific yield of this proposal, we will create a resource for future molecular genetic and follow-up studies of adult ADHD. We will set the stage for these studies by 1) providing a comprehensive baseline assessment for a follow-up study and 2) clarifying the nature of phenotypes and the sample sizes that will be needed for molecular genetic studies. Thus, if founded, we expect that the proposed work will lead to a program of research that can both clarify the nosological complexities of adult ADHD and clarify the nature of genes that are risk factors for the disorder.